Synthesis of organoselenyl isoquinolinium imidesviairon(iii) chloride-mediated tandem cyclization/selenation ofN′-(2-alkynylbenzylidene)hydrazides and diselenides

Article abstract of DOI:10.1039/d0ob01517b

This report describes the synthesis of organoselenyl isoquinolinium imides through a tandem cyclization betweenN′-(2-alkynylbenzylidene)hydrazides and diselenides. The reaction was carried out at room temperature under an ambient atmosphere using cheap iron(iii) chloride as the metallic source. The strategy shows good tolerance to a broad range ofN′-(2-alkynylbenzylidene)hydrazides and diselenides, and forms C-N and C-Se bonds in one step. The obtained product is further transformed into a bioactiveH-pyrazolo[5,1-a]isoquinoline skeleton easilyviaa silver catalyzed [3 + 2] cycloaddition.

Full text of DOI:10.1039/d0ob01517b

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Synthesis of organoselenyl isoquinolinium imides
via iron(III) chloride-mediated tandem cyclization/
selenation of N’-(2-alkynylbenzylidene)hydrazides
and diselenides†
Cite this: DOI: 10.1039/d0ob01517b
Hai-Feng Yao,a Dian-Liang Wang,a Fang-Hui Li,a Bing Wu,b Zhong-Jian Cai *a and
a
Shun-Jun Ji
*
This report describes the synthesis of organoselenyl isoquinolinium imides through a tandem cyclization
between N’-(2-alkynylbenzylidene)hydrazides and diselenides. The reaction was carried out at room
temperature under an ambient atmosphere using cheap iron(III) chloride as the metallic source. The strat-
egy shows good tolerance to a broad range of N’-(2-alkynylbenzylidene)hydrazides and diselenides, and
forms C–N and C–Se bonds in one step. The obtained product is further transformed into a bioactive
H-pyrazolo[5,1-a]isoquinoline skeleton easily via a silver catalyzed [3 + 2] cycloaddition.
Received 23rd July 2020,
Accepted 27th August 2020
DOI: 10.1039/d0ob01517b
rsc.li/obc
lyzed direct C–H bond functionalization for the efficient syn-
Introduction
thesis of phosphorus-containing isoquinolines (Fig. 1d).6
Heterocycles are important elements of organic compounds Therefore, the development of a simple and efficient method
and widely found in natural products, pharmaceuticals and for the divergent synthesis of isoquinolinium imides is still
some fine chemicals.1 Among them, isoquinoline-based struc- highly desirable.
tures represent one of the most important heterocycles due to
Selenium-containing skeletons have attracted increasing
their rich biological activities.2 Isoquinolinium imides are his- attention due to their wide diversity in drug candidates and
torically recognized as latent azomethine imines, which have functional organic materials.7 Moreover, they are also exten-
been used as useful building blocks in a range of 1,3-dipolar sively used as catalysts, ligands and synthetic intermediates in
cycloaddition events. For instance, Wu and other groups
found that isoquinolinium imides could be generated in situ,
and then used as powerful 1,3-dipoles in [3 + 2] cycloaddition
with alkynes, alkenes and arynes (Fig. 1a).3 Guo and co-
workers synthesized a series of eight-membered N,O-contain-
ing heterocycles by a formal [5 + 3] cycloaddition of isoquinoli-
nium imides with zwitterionic allylpalladium intermediates
(Fig. 1b).4 Glorius and co-workers reported an excellent strat-
egy for the asymmetric synthesis of indolizidine derivatives by
N-heterocyclic carbene (NHC) catalyzed formal [3 + 3] or [3 + 2]
cycloaddition of isoquinolinium imides with enals (Fig. 1c).5
Recently, isoquinolinium imides were applied in a copper cata-
aKey Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry,
Chemical Engineering and Materials Science & Collaborative Innovation Centre of
Suzhou Nano Science and Technology, Soochow University, 199 Ren-Ai Road,
Suzhou, Jiangsu 215123, China. E-mail: zjcai@suda.edu.cn, shunjun@suda.edu.cn;
Fax: (+)86 512 65880307
bAnalysis and Testing Center, Soochow University, 199 Ren-Ai Road, Suzhou, Jiangsu
215123, China
†Electronic supplementary information (ESI) available. CCDC 1976346. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
d0ob01517b
Fig. 1 Isoquinolinium imides used as useful building blocks.
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Table 1 Optimization of the reaction conditionsa
Entry
Solvent
2a/equiv.
[Fe]/equiv.
T/h
Yieldb/%
Fig. 2 Tandem cyclization/selenation.
1
2
3
4
5
6
7
8
DCM
MeCN
DCE
Toluene
THF
MeNO2
Dioxane
EtOH
DMF
DMA
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
2
2
2
2
2
2
2
2
2
2
1.5
1
0.5
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
1
0.5
0.2
2
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
8
84
73
97
90
13
39
12
Trace
Trace
Trace
92
88
42
38
24
13
87
organic synthesis.8 Regarding the indisputable significance of
isoquinoline and selenoether frameworks, the development of
an efficient approach for the construction of selenium-contain-
ing isoquinolinium imides is of particular interest. Tandem
cyclization/cycloaddition reactions are one of the most
efficient and useful methods for the synthesis of
heterocycles.9,10 The cascade strategies are always utilized as
powerful tools to construct complicated molecular frameworks
from relatively simple starting materials in a single vessel.
Herein, we reported an efficient synthesis of organoselenyl iso-
quinolinium imides through a tandem cyclization (Fig. 2). The
reaction used easily accessible N′-(2-alkynylbenzylidene)hydra-
zides as the starting materials, and constructed C–Se and C–N
bonds in one step with the assistance of cheap iron(III) chlor-
ide.11 The generated dipole structure provided the possibility
to further access complicated molecular frameworks.
9
10
11
12
13
14
15
16
17
18c
19d
2
2
12
12
63
23
2
a Reaction conditions: 1a (0.20 mmol, 1.0 equiv.), 2a (X equiv.), FeCl3
(Y equiv.), solvent (4.0 mL) at room temperature. b Isolated yield.
c FeCl3 (2 equiv.) was replaced by FeBr3 (2 equiv.). d FeCl3 (2 equiv.) was
replaced by AlCl3 (2 equiv.).
Results and discussion
Table 2 Substrate scope of N’-(2-alkynylbenzylidene)hydrazidesa,b
We began our research with the reaction between 4-methyl-N′-
(2-(phenylethynyl)benzylidene)benzenesulfonohydrazide (1a)
and 1,2-diphenyldiselane (2a) with the assistance of FeCl3.
Firstly, several solvents were screened briefly. It was found that
when the reaction was carried out with 0.2 mmol 1a, 0.4 mmol
2a and 0.4 mmol FeCl3 at room temperature for 12 h, DCM,
MeCN, DCE and toluene seemed to be suitable solvents
(Table 1, entries 1–4), and DCE gave the corresponding
product 3aa in up to 97% yield (entry 3). THF, MeNO2, and
dioxane could only give the desired product 3aa in 12–39%
yields (Table 1, entries 5–7). A trace amount of the product was
observed when the reaction was performed in polar solvents
such as ethanol, DMF and DMA (Table 1, entries 8–10).
Further decreasing the amount of 2a (entries 11–13) or FeCl3
(entries 14–16) had a significant negative influence on the
reaction efficiency. The desired product was obtained in a
lower yield (87%) and a trace amount of the starting material
1a remained when the reaction was completed in a shorter
time (entry 17). The tandem cyclization/selenation reaction
gave 3aa in 63% and 23% yields respectively when FeBr3 or
AlCl3 was used to replace FeCl3 (entries 18 and 19).
With the optimized reaction conditions in hand, a range of
N′-(2-alkynylbenzylidene)hydrazides were examined first. The
results are presented in Table 2. It was found that the reaction
exhibited good tolerance for a range of substituted alkynes.
The ortho-fluorine substituted substrate could also give the
corresponding isoquinolinium imide 3ha in 92% yield, and
a The reaction was conducted with 1 (0.5 mmol), 2a (1.0 mmol), FeCl3
(1.0 mmol) and DCE (4.0 mL) at room temperature. b Isolated yield.
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X-ray crystallographic diffraction of 3ha further confirmed the line conveniently by a [3 + 2] cycloaddition with alkyne
structure of the product. Notably, the reaction was not sensi- (Scheme 2). Notably, the H-pyrazolo[5,1-a]isoquinoline skel-
tive to heterocycloalkynes, and a similar yield was observed for eton exhibited important biological activities, which could be
thiophen-3-ylethynyl hydrazide 2i. Replacing the substituents used as a CDC25B inhibitor, TC-PTP inhibitor, and PTP1B
(R2) on the benzene ring of hydrazides with different func- inhibitor.12
tional groups, such as fluorine, chlorine and methoxy, resulted
in a good yield of 3ja, 3ka, 3la and 3ma, respectively.
In order to gain a mechanistic understanding of this
tandem cyclization/selenation, we conducted some control
After that, we investigated the scope of the tandem cycliza- experiments (Scheme 3). It was found that no desired product
tion/selenation with respect to diselenyl ethers (Table 3). The 3ma was observed when the reaction was performed in the
desired products were obtained in 63–96% yields when aro- absence of FeCl3 (Scheme 3a). When PhSeCl, which was
matic diselenyl ethers were subjected to the reaction of 2b–d usually synthesized by the reaction of diphenyl diselenide and
with hydrazide 1a. To our delight, 1,2-di(thiophen-3-yl)dise- thionyl chloride,13 was used instead of PhSeSePh, the sel-
lane was also compatible for this reaction (3ae). Unfortunately, enium-containing isoquinolinium imide was isolated in 95%
pyridinyldiselanes failed to generate the corresponding pro- yield (Scheme 3b). Then we reduced the loading of FeCl3 to
ducts, which may be due to the strong coordination ability of 20 mol%; to our delight, we could still obtain the corres-
pyridine. To our delight, the reaction proceeded smoothly with ponding product in 74% yield (Scheme 3c). More interestingly,
dialkyl diselanes, which gave the desired organoselenyl isoqui- a tandem cyclization/selenation product was generated in 59%
nolinium imides in 75–94% yields.14
yield in the absence of FeCl3 by using PhSeCl as the starting
The selenium-containing isoquinolinium imide was material (Scheme 3d). The desired product was obtained in
obtained on a gram scale easily, which further highlighted the 92% yield when the radical scavenger BHT (butylated hydroxy-
potential application of this tandem cyclization/selenation
strategy (Scheme 1).
Interestingly, the isoquinolinium imide could be trans-
formed into selenium-containing H-pyrazolo[5,1-a]isoquino-
Table 3 Scope of diselanesa,b
Scheme 2 [3 + 2] cycloaddition with alkyne.
a The reaction was conducted with 1a (0.5 mmol), 2 (1.0 mmol), FeCl3
(1.0 mmol) and DCE (4.0 mL) at room temperature. b Isolated yield.
Scheme 1 Gram-scale synthesis.
Scheme 3 Control experiments.
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layer was dried with anhydrous Na2SO4. Finally, the solvent
was removed by rotary evaporation and the residue was puri-
fied by column chromatography on silica gel (ethyl acetate/pet-
roleum ether = 1/3 to 2/1, v/v) to afford the corresponding
product 3ba as a yellow solid in 85% yield.
General procedure for the gram-scale synthesis of 3aa. An
over-dried round-bottom reaction flask (100 mL) equipped
with a magnetic stir bar was charged with 1a (2.0 mmol,
1 equiv.), 2a (4.0 mmol, 2 equiv.) and FeCl3 (anhydrous,
4.0 mmol, 2 equiv.). Then DCE (20 mL) was added into the
mixture. Then the reaction system was kept stirring at room
temperature (27 °C in an oil bath) for 12 h. After that, the
system was extracted with DCM twice (45 mL × 2). The com-
bined organic layer was dried with anhydrous Na2SO4. Finally,
the solvent was removed by rotary evaporation and the residue
was purified by column chromatography on silica gel (ethyl
acetate/petroleum ether = 1/3 to 2/1, v/v) to afford the corres-
ponding product 3aa as a yellow solid in 92% yield (0.9577 g).
General procedure for further modification. An over-dried
reaction tube equipped with a magnetic stir bar was charged
with 3aa (0.5 mmol, 1 equiv.), p (0.6 mmol, 1.2 equiv.), AgOTf
(10 mol%) and DBU (20 mol%). Then a mixed solvent (4 mL)
of DCE and CCl4 in a ratio of 1 : 1 was added into the mixture.
Then the reaction system was kept stirring at room tempera-
ture (27 °C in an oil bath) for 12 h. After that, the system was
extracted with DCM twice (15 mL × 2). The combined organic
layer was dried with anhydrous Na2SO4. Finally, the solvent
was removed by rotary evaporation and the residue was puri-
fied by column chromatography on silica gel (ethyl acetate/pet-
roleum ether = 1/10 to 1/3, v/v) to afford the corresponding
product 3-1 as a white solid in 47% yield.
Fig. 3 The proposed mechanism for the tandem cyclization/selenation.
toluene) was added to the reaction mixture under standard
conditions (Scheme 3e).
Based on the above experimental results and the previous
reports,11 we proposed two concomitant mechanistic routes
for the above tandem cyclization/selenation reaction. Firstly,
the reactive species PhSeFeCl2 and PhSeCl were formed
through the mixture of diphenyl diselenide and FeCl3. Then,
the triple bond of alkyne could coordinate with the iron sele-
nolate species to generate intermediate I, which underwent a
6-endo-cyclization to afford intermediate II. Finally, a reductive
elimination took place to give the selenium-containing isoqui-
nolinium imide 3aa (path A). Meanwhile, PhSeCl (4) exhibited
higher electrophilicity than PhSeSePh, and it could activate the
carbon–carbon triple bond to form intermediate III. Then a
nucleophilic attack of the nitrogen atom to the activated triple
bond could construct the final product (path B) (Fig. 3).
(3-Phenyl-4-(phenylselanyl)isoquinolin-2-ium-2-yl)(tosyl)amide
(3aa). Yellow solid. Yield 97% (102.7 mg). IR (neat) ν = 1371,
Experimental
General information
1
1280, 1132, 1087, 953, 776, 663, 589 cm−1. H NMR (400 MHz,
chloroform-d) δ 9.84 (s, 1H), 8.48 (d, J = 8.6 Hz, 1H), 8.16 (d,
All the solvents for routine isolation of products and chromato- J = 8.1 Hz, 1H), 7.89 (t, J = 7.2 Hz, 1H), 7.80 (t, J = 7.6 Hz, 1H),
graphy were reagent grade. Flash chromatography was per- 7.28 (t, J = 7.5 Hz, 1H), 7.18–7.05 (m, 7H), 6.94 (dd, J = 19.8, 7.6
formed using silica gel (200–300 mesh) with the indicated sol- Hz, 4H), 6.72 (d, J = 7.1 Hz, 2H), 2.34 (s, 3H). 13C NMR
vents. IR spectra were recorded on a spectrophotometer using (100 MHz, chloroform-d) δ 152.6, 150.2, 140.7, 140.6, 137.1,
KBr optics. 1H NMR and 13C NMR spectra were recorded on 135.2, 133.6, 131.2, 130.8, 130.3, 130.0, 129.7, 129.5, 129.1,
400 MHz (1H NMR) and 100 MHz (13C NMR) spectrometers 129.0, 128.6, 127.4, 127.3, 126.6, 21.4 ppm. 77Se NMR
using CDCl3 as the solvent and TMS as the internal standard. (76 MHz, chloroform-d) δ 353.2 ppm. HRMS (ESI) m/z: calcd
1
The H NMR data are reported as the chemical shift in parts for C28H22N2O2SSe [M + Na]+ 553.0459, found: 553.0461.
per million, multiplicity (s, singlet; d, doublet; t, triplet; q,
quartet; m, multiplet), coupling constant in hertz, and amide (3ba). Yellow solid. Yield 85% (230.0 mg). IR (neat) ν =
number of protons. High resolution mass spectra were 1477, 1373, 1281, 1082, 937, 774, 556, 457 cm−1 1H NMR
obtained using a high resolution ESI-TOF mass spectrometer (400 MHz, chloroform-d) δ 9.85 (s, 1H), 8.50 (d, J = 9.2 Hz,
and a high resolution CI-TOF mass spectrometer. 1H), 8.17 (d, J = 8.1 Hz, 1H), 7.90 (t, J = 7.1 Hz, 1H), 7.82 (t,
(4-(Phenylselanyl)-3-(m-tolyl)isoquinolin-2-ium-2-yl)(tosyl)-
.
General procedure for the generation of 3 (3ba as an J = 7.1 Hz, 1H), 7.16 (dd, J = 14.3, 7.7 Hz, 3H), 7.06 (dt, J =
example). An over-dried reaction tube equipped with a mag- 23.5, 7.5 Hz, 4H), 6.94 (dd, J = 16.7, 7.5 Hz, 4H), 6.60 (d, J =
netic stir bar was charged with 1b (0.5 mmol, 1 equiv.), 2a 7.6 Hz, 1H), 6.37 (s, 1H), 2.33 (s, 3H), 2.15 (s, 3H). 13C NMR
(1.0 mmol, 2 equiv.) and FeCl3 (anhydrous, 1.0 mmol, 2 (100 MHz, chloroform-d) δ 153.0, 150.2, 140.7, 140.6, 137.3,
equiv.). Then DCE (4 mL) was added into the mixture. Then 136.8, 135.1, 133.6, 131.5, 131.0, 130.6, 130.3, 129.9, 129.7,
the reaction system was kept stirring at room temperature 129.5, 129.3, 129.0, 127.5, 127.4, 127.2, 126.7, 21.5 ppm.
(27 °C in an oil bath) for 12 h. After that, the system was HRMS (ESI) m/z: calcd for C29H24N2O2SSe [M + Na]+ 567.0616,
extracted with DCM twice (15 mL × 2). The combined organic found: 567.0603.
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(4-(Phenylselanyl)-3-(4-propylphenyl)isoquinolin-2-ium-2-yl)
1.3 Hz, 1H), 7.87–7.83 (m, 1H), 7.16 (t, J = 7.5 Hz, 3H), 7.09 (t, J
(tosyl)amide (3ca). Yellow solid. Yield 93% (266.1 mg). IR = 7.4 Hz, 2H), 7.02–6.97 (m, 4H), 6.91–6.87 (m, 2H), 6.65 (d, J =
(neat) ν = 2359, 1281, 1136, 1086, 937, 812, 777, 659, 589 cm−1 8.5 Hz, 2H), 2.36 (s, 3H). 13C NMR (100 MHz, chloroform-d) δ
.
1H NMR (400 MHz, chloroform-d) δ 9.74 (s, 1H), 8.39 (d, J = 151.5, 150.8, 141.1, 135.5, 135.0, 131.7, 131.6, 131.1, 130.9,
8.4 Hz, 1H), 8.08 (d, J = 8.1 Hz, 1H), 7.80 (t, J = 7.8 Hz, 1H), 130.7, 129.7, 129.2, 129.1, 127.7, 127.5, 127.4, 126.6, 21.5 ppm.
7.72 (t, J = 7.6 Hz, 1H), 7.10–6.97 (m, 5H), 6.84 (dd, J = 17.7, 8.4 HRMS (ESI) m/z: calcd for C28H22ClN2O2SSe [M + H]+ 565.0250,
Hz, 6H), 6.58 (d, J = 8.1 Hz, 2H), 2.54–2.48 (m, 2H), 2.26 (s, found: 565.0259.
3H), 1.61 (h, J = 7.4 Hz, 2H), 0.93 (t, J = 7.3 Hz, 3H). 13C NMR
(100 MHz, chloroform-d) δ 152.9, 150.4, 143.3, 140.7, 140.6, (tosyl)amide (3ha). Yellow solid. Yield 92% (252.1 mg). IR
(3-(2-Fluorophenyl)-4-(phenylselanyl)isoquinolin-2-ium-2-yl)-
137.3, 135.1, 131.4, 131.0, 130.8, 130.2, 130.0, 129.9, 129.5, (neat) ν = 1613, 1438, 1280, 1132, 953, 886, 735, 666, 532 cm−1
.
129.2, 129.0, 127.4, 127.3, 126.7, 38.0, 24.4, 21.5, 14.0 ppm. 1H NMR (400 MHz, chloroform-d) δ 9.82 (s, 1H), 8.48 (d, J =
HRMS (ESI) m/z: calcd for C31H28N2O2SSe [M + Na]+ 595.0929, 8.4 Hz, 1H), 8.14 (d, J = 8.1 Hz, 1H), 7.89 (t, J = 7.4 Hz, 1H),
found: 595.0914.
7.81 (t, J = 7.5 Hz, 1H), 7.34–7.23 (m, 3H), 7.10 (dt, J = 26.0, 7.2
(3-(4-(tert-Butyl)phenyl)-4-(phenylselanyl)isoquinolin-2-ium- Hz, 3H), 7.01–6.95 (m, 4H), 6.86 (q, J = 8.5, 7.4 Hz, 2H), 6.56 (t,
2-yl)(tosyl)amide (3da). Yellow solid. Yield 92% (268.4 mg). IR J = 7.3 Hz, 1H), 2.34 (s, 3H). 13C NMR (100 MHz, chloroform-d)
(neat) ν = 2960, 2359, 1477, 1280, 1134, 951, 812, 736, 656, δ160.0 (d, JC–F = 241.7 Hz), 149.6, 147.3, 140.8, 140.5, 136.7,
529 cm−1 1H NMR (400 MHz, chloroform-d) δ 9.80 (s, 1H), 135.1, 131.6, 131.2 (d, JC–F = 7.9 Hz), 131.0, 130.7, 130.5, 129.5,
.
8.49 (d, J = 8.5 Hz, 1H), 8.16 (d, J = 8.1 Hz, 1H), 7.89 (t, J = 7.8 129.4, 129.1, 129.0, 127.6, 126.6, 123.2 (d, JC–F = 3.3 Hz), 122.0,
Hz, 1H), 7.80 (t, J = 7.6 Hz, 1H), 7.13 (d, J = 8.2 Hz, 3H), 7.05 (t, 115.1 (d, JC–F = 21.0 Hz), 21.4 ppm. 19F NMR (376 MHz, chloro-
J = 7.7 Hz, 4H), 6.91 (dd, J = 13.0, 7.6 Hz, 4H), 6.68 (d, J = 8.4 form-d) δ = −110.31 ppm (s, 1F). HRMS (ESI) m/z: calcd for
Hz, 2H), 2.34 (s, 3H), 1.35 (s, 9H). 13C NMR (100 MHz, chloro- C28H22FN2O2SSe [M + H]+ 549.0546, found: 549.0552.
form-d) δ 152.7, 151.4, 150.5, 140.7, 140.4, 137.3, 135.0, 131.2,
130.3, 130.1, 130.0, 129.4, 129.2, 129.0, 127.4, 127.3, 126.6, (tosyl)amide (3ia). Orange-red solid. Yield 81% (216.7 mg). IR
124.1, 34.7, 31.3, 21.5 ppm. HRMS (ESI) m/z: calcd for (neat) ν = 1575, 1476, 1274, 1133, 943, 863, 718, 659, 530 cm−1
C32H30N2O2SSe [M + Na]+ 609.1085, found: 609.1077. 1H NMR (400 MHz, chloroform-d) δ 9.80 (s, 1H), 8.49 (d, J =
(4-(Phenylselanyl)-3-(thiophen-3-yl)isoquinolin-2-ium-2-yl)-
.
(3-(4-Methoxyphenyl)-4-(phenylselanyl)isoquinolin-2-ium-2- 8.5 Hz, 1H), 8.15 (d, J = 8.1 Hz, 1H), 7.89 (t, J = 7.3 Hz, 1H),
yl)(tosyl)amide (3ea). Yellow solid. Yield 89% (249.8 mg). IR 7.80 (t, J = 7.5 Hz, 1H), 7.21 (d, J = 8.1 Hz, 2H), 7.12 (dd, J =
(neat) ν = 2360, 1610, 1478, 1279, 1131, 940, 810, 734, 654, 15.1, 7.5 Hz, 4H), 6.96 (dd, J = 13.6, 7.6 Hz, 4H), 6.80 (d, J = 6.0
530 cm−1 1H NMR (400 MHz, chloroform-d) δ 9.79 (s, 1H), Hz, 1H), 6.65 (dd, J = 2.8, 1.0 Hz, 1H), 2.32 (s, 3H). 13C NMR
.
8.45 (d, J = 8.4 Hz, 1H), 8.14 (d, J = 8.1 Hz, 1H), 7.89–7.84 (m, (100 MHz, chloroform-d) δ 150.6, 148.3, 140.7, 137.3, 135.2,
1H), 7.78 (t, J = 7.6 Hz, 1H), 7.19–7.05 (m, 5H), 6.96–6.91 (m, 132.8, 131.3, 130.8, 130.4, 129.6, 129.5, 129.3, 129.1, 128.7,
4H), 6.72 (d, J = 8.8 Hz, 2H), 6.61 (d, J = 8.8 Hz, 2H), 3.82 (s, 127.5, 127.2, 126.5, 123.7, 21.4 ppm. HRMS (ESI) m/z: calcd for
3H), 2.33 (s, 3H). 13C NMR (100 MHz, chloroform-d) δ 160.0, C26H20N2O2S2Se [M + Na]+ 559.0024, found: 559.0015.
152.5, 150.4, 140.8, 140.5, 137.2, 135.1, 131.7, 131.3, 130.8,
(7-Fluoro-3-phenyl-4-(phenylselanyl)isoquinolin-2-ium-2-yl)-
130.1, 129.9, 129.4, 129.1, 128.9, 127.3, 127.2, 126.5, 125.8, (tosyl)amide (3ja). Yellow solid. Yield 85% (233.1 mg). IR
112.6, 55.2, 21.3 ppm. HRMS (ESI) m/z: calcd for (neat) ν = 1482, 1278, 1130, 1113, 1086, 908, 832, 713, 655,
C29H25N2O3SSe [M + H]+ 561.0746, found: 561.0751.
532 cm−1 1H NMR (400 MHz, chloroform-d) δ 9.87 (s, 1H),
.
(3-(4-Fluorophenyl)-4-(phenylselanyl)isoquinolin-2-ium-2-yl)- 8.50 (dd, J = 9.3, 4.9 Hz, 1H), 7.81 (dd, J = 7.8, 2.4 Hz, 1H),
(tosyl)amide (3fa). Yellow solid. Yield 84% (230.6 mg). IR 7.63–7.57 (m, 1H), 7.32–7.27 (m, 1H), 7.19–7.05 (m, 7H), 6.97
(neat) ν = 1577, 1480, 1280, 1134, 953, 830, 730, 657, 534 cm−1
.
(d, J = 8.0 Hz, 2H), 6.91 (d, J = 7.5 Hz, 2H), 6.73 (d, J = 7.3 Hz,
1H NMR (400 MHz, chloroform-d) δ 9.80 (s, 1H), 8.53 (d, J = 2H), 2.34 (s, 3H). 13C NMR (100 MHz, chloroform-d) δ 162.3
8.5 Hz, 1H), 8.18 (d, J = 8.1 Hz, 1H), 7.94 (t, J = 7.8 Hz, 1H), (d, JC–F = 254.7 Hz), 152.0, 148.9, 140.8, 140.4, 134.1, 133.5,
7.84 (t, J = 7.6 Hz, 1H), 7.16 (dd, J = 13.9, 7.7 Hz, 3H), 7.08 (t, J 132.3 (d, JC–F = 8.5 Hz), 131.0, 130.9, 130.0, 129.8, 129.6, 129.1,
= 7.5 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 6.89 (d, J = 7.4 Hz, 2H), 128.7, 128.5 (d, JC–F = 10.1 Hz), 127.5, 127.4, 126.6, 125.2 (d,
6.76–6.67 (m, 4H), 2.35 (s, 3H). 13C NMR (100 MHz, chloro- JC–F = 25.0 Hz), 112.6 (d, JC–F = 22.6 Hz), 21.4 ppm. 19F NMR
form-d) δ 162.7 (d, JC–F = 247.8 Hz), 151.7, 150.6, 140.9, 140.8, (376 MHz, chloroform-d) δ = −106.25 ppm (s, 1F). HRMS (ESI)
137.4, 135.4, 132.3 (d, JC–F = 8.5 Hz), 131.0, 130.5, 130.2, 129.6, m/z: calcd for C28H21FN2O2SSe [M + Na]+ 571.0365, found:
129.4 (d, JC–F = 3.6 Hz), 129.2, 129.1, 127.6, 127.4, 126.5, 114.4 577.0377.
(d, JC–F = 21.9 Hz), 21.5 ppm. 19F NMR (376 MHz, chloroform-
d) δ = −111.60 ppm (s, 1F). HRMS (ESI) m/z: calcd for (tosyl)amide (3ka). Yellow solid. Yield 87% (238.2 mg). IR
(8-Fluoro-3-phenyl-4-(phenylselanyl)isoquinolin-2-ium-2-yl)-
C28H21FN2O2SSe [M + Na]+ 571.0365, found: 571.0378.
(neat) ν = 1576, 1477, 1285, 1120, 1083, 974, 860, 719, 659,
1
(3-(4-Chlorophenyl)-4-(phenylselanyl)isoquinolin-2-ium-2-yl)- 567 cm−1. H NMR (400 MHz, chloroform-d) δ 9.95 (d, J = 0.6
(tosyl)amide (3ga). Pale yellow solid. Yield 91% (256.6 mg). IR Hz, 1H), 8.27 (d, J = 8.6 Hz, 1H), 7.84 (td, J = 8.3, 5.6 Hz, 1H),
(neat) ν = 1575, 1478, 1280, 1133, 938, 833, 739, 654, 532 cm−1
.
7.45 (t, J = 8.5 Hz, 1H), 7.31 (t, J = 7.5 Hz, 1H), 7.23 (d, J = 8.2
1H NMR (400 MHz, chloroform-d) δ 9.77 (s, 1H), 8.54 (d, J = Hz, 2H), 7.17–7.07 (m, 5H), 6.99 (d, J = 8.0 Hz, 2H), 6.92 (d, J =
8.0 Hz, 1H), 8.18 (d, J = 8.2 Hz, 1H), 7.94 (m, J = 8.5, 7.1, 7.1 Hz, 2H), 6.77 (d, J = 7.1 Hz, 2H), 2.35 (s, 3H). 13C NMR
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(100 MHz, chloroform-d) δ 158.6 (d, JC–F = 262.2 Hz), 153.5,
(4-((3,5-Dichlorophenyl)selanyl)-3-phenylisoquinolin-2-ium-
144.1 (d, JC–F = 6.6 Hz), 141.0, 140.4, 137.7, 135.6 (d, JC–F = 8.6 2-yl)(tosyl)amide (3ad). Yellow solid. Yield 63% (188.3 mg). IR
Hz), 133.4, 131.1, 130.9, 129.9, 129.6, 129.2, 128.9, 127.7, (neat) ν = 2922, 1560, 1372, 1280, 1135, 946, 881, 755, 655,
127.5, 126.7, 125.2 (d, JC–F = 4.4 Hz), 118.6 (d, JC–F = 14.8 Hz), 533 cm−1 1H NMR (400 MHz, chloroform-d) δ 9.90 (s, 1H),
.
114.2 (d, JC–F = 18.0 Hz), 21.5 ppm. 19F NMR (376 MHz, chloro- 8.46 (d, J = 8.5 Hz, 1H), 8.23 (d, J = 8.2 Hz, 1H), 7.99 (t, J = 8.3
form-d) δ = −116.14 ppm (s, 1F). HRMS (ESI) m/z: calcd for Hz, 1H), 7.89 (t, J = 7.4 Hz, 1H), 7.30 (t, J = 7.5 Hz, 1H), 7.16 (d,
C28H21FN2O2SSe [M + H]+ 549.0546, found: 549.0551.
J = 8.1 Hz, 2H), 7.14 (t, J = 1.7 Hz, 1H), 7.09 (t, J = 7.8 Hz, 2H),
(7-Chloro-3-phenyl-4-(phenylselanyl)isoquinolin-2-ium-2-yl)- 6.98 (d, J = 8.0 Hz, 2H), 6.72 (d, J = 1.8 Hz, 2H), 6.66 (d, J = 7.3
(tosyl)amide (3la). Yellow solid. Yield 90% (254.4 mg). IR Hz, 2H), 2.35 (s, 3H). 13C NMR (100 MHz, chloroform-d) δ
1
(neat) ν = 1573, 1280, 1140, 1084, 891, 731, 659, 533 cm−1. H 152.9, 150.8, 140.9, 140.5, 136.9, 135.7, 133.3, 133.1, 130.7,
NMR (400 MHz, chloroform-d) δ 9.82 (s, 1H), 8.41 (d, J = 9.1 129.9, 129.8, 129.2, 129.0, 128.9, 128.6, 127.9, 127.5, 126.6,
Hz, 1H), 8.14 (d, J = 1.9 Hz, 1H), 7.76 (dd, J = 9.1, 2.1 Hz, 1H), 21.5 ppm. HRMS (ESI) m/z: calcd for C28H21Cl2N2O2SSe [M +
7.30 (t, J = 7.5 Hz, 1H), 7.16 (dd, J = 17.0, 7.5 Hz, 4H), 7.11–7.06 H]+ 598.9861, found: 598.9854.
(m, 3H), 6.97 (d, J = 8.1 Hz, 2H), 6.91 (d, J = 7.3 Hz, 2H), 6.74
(3-Phenyl-4-(thiophen-3-ylselanyl)isoquinolin-2-ium-2-yl)-
(d, J = 7.2 Hz, 2H), 2.34 (s, 3H). 13C NMR (100 MHz, chloro- (tosyl)amide (3ae). Orange-yellow solid. Yield 71% (191.0 mg).
form-d) δ 152.8, 148.8, 140.9, 140.4, 136.6, 135.6, 135.3, 133.4, IR (neat) ν = 1278, 1133, 1086, 952, 881, 766, 668, 530 cm−1
.
131.0, 130.9, 130.0, 129.7, 129.1, 128.9, 128.1, 127.7, 127.6, 1H NMR (400 MHz, chloroform-d) δ 9.78 (s, 1H), 8.63–8.60
127.5, 126.7, 21.5 ppm. HRMS (ESI) m/z: calcd for (m, 1H), 8.15 (d, J = 8.2 Hz, 1H), 7.97–7.92 (m, 1H), 7.84–7.80
C28H22ClN2O2SSe [M + H]+ 565.0250, found: 565.0254.
(m, 1H), 7.32 (t, J = 7.5 Hz, 1H), 7.17–7.12 (m, 5H), 6.96 (d, J =
(7-Methoxy-3-phenyl-4-(phenylselanyl)isoquinolin-2-ium-2- 7.9 Hz, 2H), 6.81 (dd, J = 2.9, 1.2 Hz, 1H), 6.75 (dd, J = 8.2,
yl)(tosyl)amide (3ma). Yellow solid. Yield 75% (209.8 mg). IR 1.1 Hz, 2H), 6.58 (dd, J = 5.0, 1.2 Hz, 1H), 2.35 (s, 3H). 13C NMR
(neat) ν = 1614, 1379, 1274, 1134, 1106, 807, 700, 653, (100 MHz, chloroform-d) δ 152.2, 150.1, 140.8, 140.6, 137.2,
534 cm−1 1H NMR (400 MHz, chloroform-d) δ 9.82 (s, 1H), 135.1, 133.5, 130.6, 130.3, 130.2, 130.0, 129.5, 129.1, 129.0, 128.8,
.
8.35 (d, J = 10.4 Hz, 1H), 7.49–7.45 (m, 2H), 7.26–7.04 (m, 8H), 127.4, 127.2, 126.9, 126.7, 122.6, 21.5 ppm. HRMS (ESI) m/z:
6.95 (d, J = 8.0 Hz, 2H), 6.89 (dd, J = 8.3, 1.2 Hz, 2H), 6.70–6.66 calcd for C26H21N2O2S2Se [M + H]+ 537.0204, found: 537.0207.
(m, 2H), 3.97 (s, 3H), 2.34 (s, 3H). 13C NMR (100 MHz,
(3-Phenyl-4-(pyridin-2-ylselanyl)isoquinolin-2-ium-2-yl)(tosyl)-
chloroform-d) δ 160.5, 150.5, 148.8, 140.7, 140.6, 133.8, 133.0, amide (3af). An unsuccessful case. We didn’t get any data
131.4, 130.7, 130.2, 129.5, 129.2, 129.0, 128.5, 128.4, 127.3, about it for the reaction didn’t occur at all.
126.6, 106.2, 56.2, 21.4 ppm. HRMS (ESI) m/z: calcd for
(3-Phenyl-4-(pyridin-3-ylselanyl)isoquinolin-2-ium-2-yl)(tosyl)-
amide (3ag). An unsuccessful case. We didn’t get any data
C29H24N2O3SSe [M + Na]+ 583.0565, found: 583.0566.
(4-((4-Methoxyphenyl)selanyl)-3-phenylisoquinolin-2-ium-2- about it for the reaction didn’t occur at all.
yl)(tosyl)amide (3ab). Orange solid. Yield 95% (265.8 mg). IR (4-(Benzylselanyl)-3-phenylisoquinolin-2-ium-2-yl)(tosyl)amide
(neat) ν = 2922, 1490, 1278, 1136, 943, 817, 759, 654, 533 cm−1
(3ah). Orange solid. Yield 75% (204.9 mg). IR (neat) ν = 1275,
.
1
1H NMR (400 MHz, chloroform-d) δ 9.77 (s, 1H), 8.58 (d, J = 1134, 1085, 948, 883, 758, 657, 533 cm−1. H NMR (400 MHz,
8.5 Hz, 1H), 8.13 (d, J = 8.2 Hz, 1H), 7.91 (t, J = 7.8 Hz, 1H), chloroform-d) δ 9.72 (s, 1H), 8.49 (d, J = 8.5 Hz, 1H), 8.12 (d,
7.80 (t, J = 7.6 Hz, 1H), 7.31 (t, J = 7.5 Hz, 1H), 7.17–7.11 (m, J = 8.1 Hz, 1H), 7.94 (t, J = 7.7 Hz, 1H), 7.82 (t, J = 7.6 Hz, 1H),
4H), 6.96 (d, J = 8.1 Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H), 6.75 (d, J = 7.32 (t, J = 7.5 Hz, 1H), 7.16–7.10 (m, 4H), 7.03 (dt, J = 14.4, 7.0
7.3 Hz, 2H), 6.62 (d, J = 8.8 Hz, 2H), 3.71 (s, 3H), 2.35 (s, 3H). Hz, 3H), 6.95 (d, J = 8.0 Hz, 2H), 6.62 (t, J = 8.5 Hz, 4H), 3.70 (s,
13C NMR (100 MHz, chloroform-d) δ 159.6, 152.2, 149.9, 140.7, 2H), 2.35 (s, 3H). 13C NMR (100 MHz, chloroform-d) δ 153.0,
137.2, 135.0, 133.8, 133.6, 130.4, 130.2, 129.5, 129.2, 129.1, 149.7, 140.6, 137.8, 136.8, 134.9, 133.7, 130.4, 130.2, 129.4,
128.7, 127.4, 126.7, 120.9, 115.2, 55.4, 21.5 ppm. HRMS (ESI) 129.1, 129.0, 128.6, 128.4, 127.3, 127.2, 126.9, 126.7, 33.7,
m/z: calcd for C29H24N2O3SSe [M + Na]+ 583.0565, found: 21.5 ppm. HRMS (ESI) m/z: calcd for C29H25N2O2SSe [M + H]+
583.0566.
545.0796, found: 545.0795.
(4-((3-Methoxyphenyl)selanyl)-3-phenylisoquinolin-2-ium-2-
(4-(Hexylselanyl)-3-phenylisoquinolin-2-ium-2-yl)(tosyl)amide
yl)(tosyl)amide (3ac). Yellow solid. Yield 96% (269.0 mg). IR (3ai). Pale yellow solid. Yield 94% (254.7 mg). IR (neat) ν =
1
(neat) ν = 2928, 1574, 1477, 1280, 1137, 951, 833, 780, 682, 2933, 1480, 1292, 1135, 943, 880, 761, 661, 534 cm−1. H NMR
531 cm−1 1H NMR (400 MHz, chloroform-d) δ 9.84 (s, 1H), (400 MHz, chloroform-d) δ 9.75 (s, 1H), 8.63 (d, J = 8.5 Hz,
.
8.48 (d, J = 8.5 Hz, 1H), 8.16 (d, J = 8.1 Hz, 1H), 7.90 (t, J = 1H), 8.15 (d, J = 8.2 Hz, 1H), 8.00 (t, J = 7.8 Hz, 1H), 7.84 (t, J =
7.7 Hz, 1H), 7.81 (t, J = 7.6 Hz, 1H), 7.20–6.95 (m, 8H), 6.73 7.6 Hz, 1H), 7.34 (t, J = 7.5 Hz, 1H), 7.18 (t, J = 8.8 Hz, 4H), 6.96
(d, J = 7.7 Hz, 2H), 6.67 (d, J = 8.3 Hz, 1H), 6.51–6.45 (m, 2H), (d, J = 8.0 Hz, 2H), 6.89 (d, J = 7.7 Hz, 2H), 2.46 (t, J = 7.3 Hz,
3.64 (s, 3H), 2.34 (s, 3H). 13C NMR (100 MHz, chloroform-d) 2H), 2.35 (s, 3H), 1.32–1.06 (m, 8H), 0.79 (t, J = 7.1 Hz, 3H). 13
C
δ 160.0, 152.7, 150.3, 140.7, 140.6, 137.3, 135.2, 133.6, NMR (100 MHz, chloroform-d) δ 152.2, 149.4, 140.8, 140.7,
132.2, 130.4, 130.3, 130.0, 129.6, 129.5, 129.2, 129.1, 128.7, 137.8, 134.9, 133.6, 130.6, 130.2, 129.9, 129.5, 129.2, 129.1,
127.4, 126.7, 123.1, 116.6, 112.8, 55.3, 21.5 ppm. HRMS (ESI) 128.7, 127.4, 127.1, 126.7, 31.1, 30.8, 30.0, 29.2, 22.5, 21.5,
m/z: calcd for C29H24N2O3SSe [M + Na]+ 583.0565, found: 14.0 ppm. HRMS (ESI) m/z: calcd for C28H31N2O2SSe [M + H]+
583.0565.
539.1266, found: 539.1284.
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(4-(Octylselanyl)-3-phenylisoquinolin-2-ium-2-yl)(tosyl)amide
Chem. Rev., 2004, 104, 2239–2258; (c) A. Deiters and
S. F. Martin, Chem. Rev., 2004, 104, 2199–2238; (d) S. Süzen,
Top. Heterocycl. Chem., 2007, 11, 145–178; (e) Z. Jakopin
and M. S. Dolenc, Curr. Med. Chem., 2010, 17, 651–671;
(f) J.-R. Chen, X.-Q. Hu, L.-Q. Lu and W.-J. Xiao, Chem. Rev.,
2015, 115, 5301–5365; (g) J. Xuan and A. Studer, Chem. Soc.
Rev., 2017, 46, 4329–4346.
2 For selected cases, see: (a) K. W. Bentley, The Isoquinoline
Alkaloids, Harwood Academic, Australia, 1998, vol. 1;
(b) P. Ramesh, N. S. Reddy and Y. Venkateswarlu, J. Nat.
Prod., 1999, 62, 780–781; (c) T. Kaneda, Y. Takeuchi,
H. Matsui, K. Shimizu, N. Urakawa and S. Nakajyo,
J. Pharmacol. Sci., 2005, 98, 275–282; (d) C. Marchand,
S. Antony, K. W. Kohn, M. Cushman, A. Ioanoviciu,
B. L. Staker, A. B. Burgin, L. Stewart and Y. Pommier, Mol.
Cancer Ther., 2006, 5, 287–295; (e) B. W. Trotter,
K. K. Nanda, N. R. Kett, C. P. Regan, J. J. Lynch,
G. L. Stump, L. Kiss, J. Wang, R. H. Spencer, S. A. Kane,
R. B. White, R. Zhang, K. D. Anderson, N. J. Liverton,
C. J. McIntyre, D. C. Beshore, G. D. Hartman and
C. J. Dinsmore, J. Med. Chem., 2006, 49, 6954–6957.
3 (a) Z. Chen, X. Yang and J. Wu, Chem. Commun., 2009,
3469–3471; (b) Z. Chen, M. Su, X. Yu and J. Wu, Org.
Biomol. Chem., 2009, 7, 4641–4646; (c) J. Zhao, C. Wu, P. Li,
W. Ai, H. Chen, C. Wang, R. C. Larock and F. Shi, J. Org.
Chem., 2011, 76, 6837–6843; (d) C. Wu, Q. Wang, J. Zhao,
P. Li and F. Shi, Synthesis, 2012, 44, 3033–3042; (e) X. Gong
and J. Wu, Org. Biomol. Chem., 2015, 13, 11657–11662;
(f) X. Cheng, X. Cao, J. Xuan and W.-J. Xiao, Org. Lett.,
2018, 20, 52–55.
(3aj). Pale yellow solid. Yield 90% (255.1 mg). IR (neat) ν =
1
2923, 1372, 1291, 1136, 941, 879, 762, 655, 533 cm−1. H NMR
(400 MHz, chloroform-d) δ 9.77 (s, 1H), 8.62 (d, J = 7.9 Hz,
1H), 8.16 (d, J = 8.1 Hz, 1H), 8.01 (t, J = 7.8 Hz, 1H), 7.84 (t, J =
8.1 Hz, 1H), 7.34 (t, J = 7.5 Hz, 1H), 7.18 (t, J = 8.1 Hz, 4H), 6.97
(d, J = 8.0 Hz, 2H), 6.89 (d, J = 7.1 Hz, 2H), 2.47 (t, J = 7.3 Hz,
2H), 2.35 (s, 3H), 1.28–1.04 (m, 12H), 0.84 (t, J = 7.1 Hz, 3H).
13C NMR (100 MHz, chloroform-d) δ 151.9, 149.4, 140.6, 140.5,
137.6, 134.9, 133.7, 130.4, 130.2, 129.7, 129.4, 129.0, 128.9,
128.5, 127.2, 126.9, 126.5, 31.6, 30.6, 29.8, 29.3, 28.9, 28.7,
22.5, 21.3, 14.0 ppm. HRMS (ESI) m/z: calcd for
C30H34N2O2SSe [M + Na]+ 589.1398, found: 589.1355.
2,5-Diphenyl-6-(phenylselanyl)pyrazolo[5,1-a]isoquinoline
(3-1). White solid. Yield 47% (56.1 mg). 1H NMR (400 MHz,
chloroform-d) δ 8.43 (d, J = 8.3 Hz, 1H), 8.20 (d, J = 7.0 Hz,
1H), 7.92 (d, J = 7.0 Hz, 2H), 7.61 (t, J = 6.9 Hz, 1H), 7.55 (d, J =
6.9 Hz, 1H), 7.51 (s, 5H), 7.43–7.39 (m, 3H), 7.37–7.33 (m, 1H),
7.14 (m, J = 8.2, 5.2, 2.7 Hz, 5H). 13C NMR (100 MHz, chloro-
form-d) δ 153.2, 144.5, 140.9, 135.3, 133.4, 133.1, 130.5, 130.4,
129.6, 129.3, 129.1, 129.0, 128.7, 128.5, 128.0, 127.9, 126.6,
126.1, 124.4, 123.9, 112.4, 95.3 ppm. HRMS (CI) m/z: calcd for
C29H21N2Se [M + H]+ 477.0864, found: 477.0869.
Conclusions
In summary, we have developed an efficient iron(III) chloride
promoted tandem cyclization/selenation method to construct
a selenium-containing isoquinolinium imide skeleton. The
reaction was carried out under mild and ambient atmosphere
conditions by using easily accessible N′-(2-alkynylbenzylidene)
hydrazides and diselenides as starting materials. The gener-
ated N-iminoisoquinolinium ylides are useful building blocks,
which could be transformed into other more complex sel-
enium-containing heterocycles easily.
4 C. Yuan, Y. Wu, D. Wang, Z. Zhang, C. Wang, L. Zhou,
C. Zhang, B. Song and H. Guo, Adv. Synth. Catal., 2018,
360, 652–658.
5 C. Guo, M. Fleige, D. Janssen-Müller, C. G. Daniliuc and
F. Glorius, Nat. Chem., 2015, 7, 842–847.
6 X.-C. Zhan, Y.-Y. Hei, J.-L. Song, P.-C. Qian, X.-G. Zhang
and C.-L. Deng, Org. Chem. Front., 2019, 6, 1453–1457.
7 (a) A. Muller, E. Cadenas, P. Graf and H. Sies, Biochem.
Pharmacol., 1984, 33, 3235–3239; (b) H. J. Reich and
C. P. Jasperse, J. Am. Chem. Soc., 1987, 109, 5549–5551;
(c) M. Parnham and H. Sies, Expert Opin. Invest. Drugs,
2000, 9, 607–619; (d) C. Jacob, G. I. Giles, N. M. Giles and
H. Sies, Angew. Chem., Int. Ed., 2003, 42, 4742–4758;
(e) C. W. Nogueira, G. Zeni and J. B. T. Rocha, Chem. Rev.,
2004, 104, 6255–6285; (f) B. K. Sarma and G. Mugesh,
J. Am. Chem. Soc., 2005, 127, 11477–11485; (g) B. K. Sarma,
D. Manna, M. Minoura and G. Mugesh, J. Am. Chem. Soc.,
2010, 132, 5364–5374; (h) A. C. Terentis, M. Freewan,
T. S. S. Plaza, M. J. Raftery, R. Stocker and S. R. Thomas,
Biochemistry, 2010, 49, 591–600.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
We gratefully acknowledge the National Natural Science
Foundation of China (21672157), PAPD, the project of scienti-
fic and technologic infrastructure of Suzhou (SZS201708), and
Soochow University (Q410900620) for financial support. We
thank Qing Yuan in the Ji’s group for repeating the results.
8 For selected examples, see: (a) S. S. Khokhar and T. Wirth,
Angew. Chem., Int. Ed., 2004, 43, 631–633; (b) K. Okamoto,
Y. Nishibayashi, S. Uemura and A. Toshimitsu, Angew.
Chem., Int. Ed., 2005, 44, 3588–3591; (c) S. A. Shahzad and
T. Wirth, Angew. Chem., Int. Ed., 2009, 48, 2588–2591;
(d) D. M. Freudendahl, S. Santoro, S. A. Shahzad, C. Santi
Notes and references
1 For selected reviews, see: (a) F. Alonso, I. P. Beletskaya
and M. Yus, Chem. Rev., 2004, 104, 3079–3159;
(b) M. D. McReynolds, J. M. Dougherty and P. R. Hanson,
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Org. Biomol. Chem.

View Article Online
Paper
and T. Wirth, Angew. Chem., Int. Ed., 2009, 48, 8409–8411;
Organic & Biomolecular Chemistry
X.-Z. Shu, J. Chen, S.-C. Zhao, Z.-J. Zheng, L. Lu, X.-Y. Liu
and Y.-M. Liang, Org. Lett., 2008, 10, 3919–3922;
( j) Z.-J. Cai, C. Yang, S.-Y. Wang and S.-J. Ji, Chem.
Commun., 2015, 51, 14267–14270.
(e) J. Trenner, C. Depken, T. Weber and A. Breder, Angew.
Chem., Int. Ed., 2013, 52, 8952–8956; (f) R. Guo, J. Huang,
H. Huang and X. Zhao, Org. Lett., 2016, 18, 504–507.
9 For reviews, see: (a) J. Montgomery, Angew. Chem., Int. Ed., 11 (a) L. Yu, L. Ren, R. Yi, Y. Wu, T. Chen and R. Guo,
2004, 43, 3890–3908; (b) E. Negishi, C. Coperet, S. Ma,
S. Y. Liou and F. Liu, Chem. Rev., 1996, 96, 365–394;
(c) L. F. Tietze, Chem. Rev., 1996, 96, 115–136; (d) R. Grigg
and V. Sridharan, J. Organomet. Chem., 1999, 576, 65–87;
(e) T. Miura and M. Murakami, Chem. Commun., 2007, 217–
224.
J.
Organomet.
Chem.,
2011,
696,
2228–2233;
(b) T. Prochnow, D. F. Back and G. Zeni, Adv. Synth. Catal.,
2016, 358, 1119–1129; (c) A. Speranca, B. Godoi and
G. Zeni, J. Org. Chem., 2013, 78, 1630–1637; (d) A. L. Stein,
F. N. Bilheri;, D. F. Back and G. Zeni, Adv. Synth. Catal.,
2014, 356, 501–508; (e) A. M. S. Recchi, D. F. Back and
G. Zeni, J. Org. Chem., 2017, 82, 2713–2723;
(f) R. D. C. Pinheiro, D. F. Back and G. Zeni, Adv. Synth.
Catal., 2019, 361, 1866–1873; (g) H.-F. Yao, F.-H. Li, J. Li,
S.-Y. Wang and S.-J. Ji, Org. Biomol. Chem., 2020, 18, 1987–
1993; (h) K. K. Casola, M. R. Gomes, D. F. Back and
G. Zeni, J. Org. Chem., 2020, 85, 7349–7357.
10 For selected examples, see: (a) J. A. Porco Jr.,
F. J. Schoenen, T. J. Stout, J. Clardy and S. L. Schreiber,
J. Am. Chem. Soc., 1990, 112, 7410–7411; (b) G. A. Molander
and C. R. Harris, J. Am. Chem. Soc., 1996, 118, 4059–4071;
(c) C. Chen, M. E. Layton, S. M. Sheehan and M. D. Shair,
J. Am. Chem. Soc., 2000, 122, 7424–7425; (d) K. Agapiou,
D. F. Cauble and M. J. Krische, J. Am. Chem. Soc., 2004, 12 Z. Chen and J. Wu, Org. Lett., 2010, 12, 4856–4859.
126, 4528–4529; (e) K. Subburaj and J. Montgomery, J. Am. 13 W. J. E. Parr, J. Chem. Soc., Perkin Trans. 1, 1981, 3002.
Chem. Soc., 2003, 125, 11210–11211; (f) H.-C. Guo and 14 It was found that a trace amount of the desired product
J.-A. Ma, Angew. Chem., Int. Ed., 2006, 45, 354–366;
(g) F. Shi, X. Li, Y. Xia, L. Zhang and Z.-Y. Yu, J. Am. Chem.
Soc., 2007, 129, 15503–15512; (h) S. W. Youn, J.-Y. Song and
D. I. Jung, J. Org. Chem., 2008, 73, 5658–5661; (i) K.-G. Ji,
was observed by LCMS when 1,2-diphenylditellane was
treated under standard conditions, and the tandem cycliza-
tion/thiolation product was obtained in 8% yield when 1,2-
diphenyldisulfane was used.
Org. Biomol. Chem.
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